Laboratory of Topological Methods in Dynamics, National Research University High School of Economics, Nizhny Novgorod, 25/12 Bolshay Pecherskaya str., Nizhny Novgorod 603155, Russia.
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Str. 11, Dortmund, Germany.
Chaos. 2020 Jan;30(1):013144. doi: 10.1063/1.5127107.
The cooperative dynamics of cellular populations emerging from the underlying interactions determines cellular functions and thereby their identity in tissues. Global deviations from this dynamics, on the other hand, reflect pathological conditions. However, how these conditions are stabilized from dysregulation on the level of the single entities is still unclear. Here, we tackle this question using the generic Hodgkin-Huxley type of models that describe physiological bursting dynamics of pancreatic β-cells and introduce channel dysfunction to mimic pathological silent dynamics. The probability for pathological behavior in β-cell populations is ∼100% when all cells have these defects, despite the negligible size of the silent state basin of attraction for single cells. In stark contrast, in a more realistic scenario for a mixed population, stabilization of the pathological state depends on the size of the subpopulation which acquired the defects. However, the probability to exhibit stable pathological dynamics in this case is less than 10%. These results, therefore, suggest that the physiological bursting dynamics of a population of β-cells is cooperatively maintained, even under intercellular communication defects induced by dysfunctional channels of single cells.
细胞群体的合作动力学源自潜在的相互作用，决定了细胞的功能，从而决定了它们在组织中的身份。另一方面，全局偏离这种动力学反映了病理状况。然而，这些条件如何在单个实体的失调水平上稳定下来仍然不清楚。在这里，我们使用描述胰腺β细胞生理爆发动力学的通用 Hodgkin-Huxley 类型的模型来解决这个问题，并引入通道功能障碍来模拟病理沉默动力学。当所有细胞都有这些缺陷时，β细胞群体中出现病理行为的概率约为 100%，尽管单个细胞的沉默状态吸引域非常小。相比之下，在更现实的混合群体情况下，病理状态的稳定取决于获得缺陷的亚群的大小。然而，在这种情况下表现出稳定的病理动力学的概率小于 10%。因此，这些结果表明，即使在单个细胞功能障碍的通道引起的细胞间通信缺陷下，β细胞群体的生理爆发动力学也能协同维持。
